Angiogenesis enables the formation of blood vessels in physiological and pathological states ranging from wound healing to cancer. Angiogenesis modulation is both location and stimuli dependent, and each instance may involve a unique combination of regulatory molecules.
The inability to vascularize engineered organs and to revascularize areas of infarction has been a major roadblock to delivering successful regenerative medicine therapies to the clinic. The ability to modulate angiogenesis in a determinant fashion would have a significant impact in a wide range of clinical applications from defining normal and pathological vascular physiology, regeneration of tissues/organs, wound healing, infarct tissue repair and the inhibition of cancer. A variety of different approaches have been taken to initiate angiogenesis and drive larger vessel formation, including direct cell seeding (mono and co-cultures), use of stem cells, and combinations of human-derived modulators/growth factors. To date there has been little success translating these in vitro approaches, which typically use non-human animal compounds, to the clinic due to their discrete protein makeup, non-human derivation, tumor-derivation, or lack of genetic regulation in the case of methods to control gene expression.
Current methods to induce in vitro angiogenesis are made of simple combinations of human-derived modulators, use animal-derived stimulators, or are entirely dependent on the use of live animals for evaluation. Using these current in vitro models made of simple combinations of human-derived and/or animal derived modulators to test potential angiogenesis inhibiting drugs constrains the screening process because they fail to represent the broad set of human in vivo molecular interactions. Regulation of only selected molecular pathways also confines attempts to prevascularize engineered organs since modulating angiogenesis requires induction of many metabolic pathways. Also, currently, the most popular and successful approach employs Matrigel™, a material derived from Engelbreth-Holm-Swarm mouse sarcoma cells, which is considered inappropriate for human therapies. Thus, an improved human-based method to induce and modulate angiogenesis could spur both pharmaceutical development and regenerative medicine.